Exome sequencing as a tool for Mendelian disease gene discovery

2011 ◽  
Vol 12 (11) ◽  
pp. 745-755 ◽  
Author(s):  
Michael J. Bamshad ◽  
Sarah B. Ng ◽  
Abigail W. Bigham ◽  
Holly K. Tabor ◽  
Mary J. Emond ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Disease Gene ◽  
Gene Discovery ◽  
Mendelian Disease ◽  
Disease Gene Discovery

scholarly journals First-line exome sequencing in Palestinian and Israeli Arabs with neurological disorders is efficient and facilitates disease gene discovery

2020 ◽  
Vol 28 (8) ◽  
pp. 1034-1043 ◽  
Author(s):  
Holger Hengel ◽  
Rebecca Buchert ◽  
Marc Sturm ◽  
Tobias B. Haack ◽  
Yvonne Schelling ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Neurological Disorders ◽  
Disease Gene ◽  
Gene Discovery ◽  
First Line ◽  
Disease Gene Discovery ◽  
Israeli Arabs

scholarly journals An integrated clinical program and crowdsourcing strategy for genomic sequencing and Mendelian disease gene discovery

2018 ◽  
Vol 3 (1) ◽  
Author(s):  
Alireza Haghighi ◽  
◽  
Joel B. Krier ◽  
Agnes Toth-Petroczy ◽  
Christopher A. Cassa ◽  
...  
Keyword(s):  
Disease Gene ◽  
Gene Discovery ◽  
Genomic Sequencing ◽  
Mendelian Disease ◽  
Disease Gene Discovery ◽  
Clinical Program

scholarly journals Human and mouse essentiality screens as a resource for disease gene discovery

2019 ◽  
Author(s):  
Pilar Cacheiro ◽  
Violeta Muñoz-Fuentes ◽  
Stephen A. Murray ◽  
Mary E. Dickinson ◽  
Maja Bucan ◽  
...  
Keyword(s):  
Developmental Disorders ◽  
Disease Gene ◽  
De Novo ◽  
Genetic Diseases ◽  
Gene Discovery ◽  
Tissue Expression ◽  
Human Cell Line ◽  
Disease Genes ◽  
Mendelian Disease ◽  
Disease Gene Discovery

ABSTRACTAlthough genomic sequencing has been transformative in the study of rare genetic diseases, identifying causal variants remains a considerable challenge that can be addressed in part by new gene-specific knowledge. Here, we integrate measures of how essential a gene is to supporting life, as inferred from the comprehensive viability and phenotyping screens performed on knockout mice by the International Mouse Phenotyping Consortium and from human cell line essentiality screens. We propose a novel, cross-species gene classification across the Full Spectrum of Intolerance to Loss-of-function (FUSIL) and demonstrate that genes in five mutually exclusive FUSIL categories have differing characteristics in the biological processes they regulate, tissue expression levels and human mutation rates. Most notably, Mendelian disease genes, particularly those associated with developmental disorders, are highly overrepresented in the developmental lethal category, representing genes not essential for cell survival but required for organism development. Exploiting this finding, we have screened developmental disorder cases from three independent disease sequencing consortia and identified potentially pathogenic, de novo variants shared in different patients for several developmental lethal genes that have not previously been associated with rare disease. We therefore propose FUSIL as an efficient resource for disease gene discovery.

scholarly journals GRIPT: A novel case-control analysis method for Mendelian disease gene discovery

2018 ◽  
Author(s):  
Jun Wang ◽  
Li Zhao ◽  
Xia Wang ◽  
Yong Chen ◽  
Mingchu Xu ◽  
...  
Keyword(s):  
Disease Gene ◽  
Gene Discovery ◽  
Case Control ◽  
Mendelian Disease ◽  
Control Analysis ◽  
Mendelian Diseases ◽  
Disease Gene Discovery ◽  
Main Challenge ◽  
Case Control Analysis ◽  
Ngs Data

AbstractDespite rapid progress of next-generation sequencing (NGS) technologies, the disease-causing genes underpinning about 50% of Mendelian diseases remain elusive. One main challenge is the high genetic heterogeneity of Mendelian diseases in which similar phenotypes are caused by different genes and each gene only accounts for a small proportion of the patients. To overcome this gap, we developed a novel method, the Gene Ranking, Identification and Prediction Tool (GRIPT), for performing case-control analysis of NGS data. Analyses of simulated and real datasets show that GRIPT is well-powered for disease gene discovery, especially for diseases with high locus heterogeneity.

scholarly journals GRIPT: a novel case-control analysis method for Mendelian disease gene discovery

2018 ◽  
Vol 19 (1) ◽  
Author(s):  
Jun Wang ◽  
Li Zhao ◽  
Xia Wang ◽  
Yong Chen ◽  
Mingchu Xu ◽  
...  
Keyword(s):  
Disease Gene ◽  
Gene Discovery ◽  
Case Control ◽  
Mendelian Disease ◽  
Control Analysis ◽  
Analysis Method ◽  
Disease Gene Discovery ◽  
Case Control Analysis
Sign in / Sign up

Export Citation Format

Share Document